Selective electrical stimulation of low versus high diameter myelinated fibers and its application in pain relief: a modeling study

Electrical stimulation of peripheral nerve fibers has always been an attractive field of research. Due to the higher activation threshold, the stimulation of small fibers is accompanied by the stimulation of larger ones. It is therefore necessary to design a specific stimulation theme in order to only activate narrow fibers. There is evidence that stimulating Aδ fibers can activate endogenous pain-relieving mechanisms. However, both selective stimulation and reducing pain by activating small nociceptive fibers are still poorly investigated. In this study, using high-frequency stimulation waveforms (5-20 kHz), computational modeling provides a simple framework for activating narrow nociceptive fibers. Additionally, a model of myelinated nerve fibers is modified by including sodium-potassium pump and investigating its effects on neuronal stimulation. Besides, a modified mathematical model of pain processing circuits in the dorsal horn is presented that consists of supraspinal pain control mechanisms. Hence, by employing this pain-modulating model, the mechanism of the reduction of pain by activating nociceptive fibers is explored. In the case of two fibers with the same distance from the point source electrode, a single stimulation waveform is capable of blocking one large fiber and stimulating another small fiber. Noteworthy, the Na/K pump model demonstrated that it does not have a significant effect on the activation threshold and firing frequency of fiber. Ultimately, results suggest that the descending pathways of Locus coeruleus may effectively contribute to pain relief through stimulation of nociceptive fibers, which will be beneficial for clinical interventions.